Stein Gundersen

The prognostic value of p53 and c‐erb b‐2 immunostaining is overrated for patients with lymph node negative breast carcinoma

Approximately 30% of breast carcinoma patients with negative lymph nodes die of their disease. Biologic markers such p53 protein and c‐erb B‐2 have been related to tumor progression, but their prognostic value remains controversial.

Droloxifene--a new anti-estrogen. A phase II study in advanced breast cancer.

Twenty-six patients with advanced breast cancer were treated with a new anti-estrogen, Droloxifene (3-hydroxy-tamoxifen). They had all used tamoxifen either in the adjuvant or the advanced situation. The dose schedule was 100 mg orally daily. Partial remissions were observed in 4 (15%) of the patients, and in another 5 patients stable disease (greater than 24 weeks of duration) was observed. Three of the responders were resistant to tamoxifen. Fourteen of the 26 patients had no side-effect. In 2 patients therapy had to be stopped due to fatigue. Droloxifene seems to be an interesting new anti-estrogen which should be further exploited.

Toremifene, a new antiestrogenic compound in the treatment of metastatic mammary cancer. A phase II study

Toremifene is a new antiestrogenic compound. Toremifene has definite antitumor effect in advanced breast cancer. The response rate in the present phase II study among postmenopausal women, mostly not pretreated with systemic therapy and with ER positive or not determined ER status in tumor tissue, was 11/23 (48%; 95% confidence interval 37-59%) including 6 complete responses. The toxicity profile was similar to that of tamoxifen. It is concluded that toremifene is at least as active as tamoxifen in advanced breast cancer and that a randomized study between these two antiestrogens is indicated.

Interferon in combination with vinblastine in advanced malignant melanoma. A phase I–II study

Nineteen patients with advanced malignant melanoma were treated with a combination of recombinant alfa‐interferon (α‐IFN) and vinblastine (VBL). The α‐IFN was administered subcutaneously daily at an initial dose of 3 × 106 IU escalating to a maximal dose of 9 × 106 U daily for the first 10 weeks followed by 3 ×/week for 6 months. The VBL was given once every week at a dose of 0.025 mg/kg. Of the 19 patients 17 were evaluable for tumor response. Thirteen patients had received chemotherapy previously. Median performance status (World Health Organization) was 0, ranging from 0 to 2. One complete response and one partial response was observed. All patients experienced flu‐like symptoms attributed to α‐IFN. Leukopenia was observed in 12 patients and a planned dose escalation of VBL was undertaken for the patients only. It is concluded that combined α‐IFN and VBL is only marginally effective in patients with advanced malignant melanoma who have had prior chemotherapy.

Influence of Droloxifene on Metastatic Breast Cancer as First-Line Endocrine Treatment

The effect of droloxifene (3-hydroxytamoxifen) given as first-line endocrine treatment was evaluated in 39 postmenopausal women with advanced receptor-positive or receptor-unknown breast cancer. The patients had not received any previous anticancer therapy apart from adjuvant treatment. The overall response rate (CR + PR) was 51% (8% CR, 43% PR), 95% confidence interval+/-15.7%. Median time to progression (all patients) was 8 months, the median time to response 2 months, while the median duration of response was 10 months. The drug was well tolerated with no major side effects recorded; 16% of the patients experienced hot flushes. The response to droloxifene recorded in the present study is in accordance with the response rates to tamoxifen as first-line treatment in identical groups of patients.

Chemotherapy with or without high-dose medroxyprogesterone acetate in oestrogen-receptor-negative advanced breast cancer

In a randomised study 142 patients with advanced oestrogen-receptor-negative breast cancer in the tumour tissue received chemotherapy alone or chemotherapy combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 126 fully evaluable for response, the response rates were 46% for chemotherapy alone and 73% for chemotherapy with HD-MPA (P = 0.005). There was no significant difference with regard to duration of response. Of the 138 patients evaluable for survival and toxicity, survival was shorter in the combined treatment group; median survival of 9 versus 13 months (P less than 0.05). Considerable toxicity was seen from HD-MPA, especially weight gain and fluid retention. The present study provides evidence that in concordance with preclinical studies an interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. The side-effects from MPA were substantial, however, and the survival data are of great concern.

Weekly doxorubicin with or without high-dose medroxyprogesterone acetate in hormone-resistant advanced breast cancer. A randomised study

In a randomised study, 218 patients with advanced breast cancer, resistant to hormone therapy, received either doxorubicin 20 mg every week (Awkly) alone or Awkly combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 210 evaluable patients, the response rates were 26% [95% confidence interval (CI) 18-34%] for Awkly and 38% (95% CI 29-47%) for Awkly + HD-MPA (P = 0.08). There was no significant difference with regard to duration of response. Median survival was 11 months in both groups. Considerable toxicity was seen from HD-MPA, particularly weight gain and fluid retention. The present study provides evidence that, in concordance with preclinical studies and a previous randomised study, interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. For further studies, other gestagens and/or a dose reduction could be investigated.

Intra-arterial infusion of mitomycin C in treatment of breast cancer: Occurrence of skin necrosis in irradiated patients

Eight previously irradiated breast cancer patients with local recurrences were treated with intra-arterial infusions of 8 mg/m2 mitomycin C given at 3-week intervals. The mean time interval between radiotherapy and intra-arterial chemotherapy was 38 months (range 2-60). In five cases a temporary reduction in tumour size was observed. However, in 3 of the 8 patients severe local pain, starting immediately after the third course of treatment, was followed 4 weeks later by the development of deep necrotic ulcers of the chest wall. These cases are reported here and discussed in relation to the results of previous studies.